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Human induced pluripotent stem cells improve recovery in stroke-injured aged rats.

Tatarishvili, Jemal LU ; Oki, Koichi LU ; Monni, Emanuela LU ; Koch, Philipp ; Memanishvili, Tamar LU ; Buga, Ana-Maria ; Verma, Vivek LU ; Popa-Wagner, Aurel ; Brüstle, Oliver and Lindvall, Olle LU , et al. (2014) In Restorative Neurology and Neuroscience 32(4). p.547-558
Abstract
Purpose: Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke. Methods: Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage. After 48 h, animals were transplanted intracortically with human iPSC-derived long-term neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke and were vehicle-injected. Results: Cell-grafted animals performed better than vehicle-injected... (More)
Purpose: Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke. Methods: Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage. After 48 h, animals were transplanted intracortically with human iPSC-derived long-term neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke and were vehicle-injected. Results: Cell-grafted animals performed better than vehicle-injected recipients in cylinder test at 4 and 7 weeks. At 8 weeks, cell proliferation was low (0.7 %) and number of hiPSC-lt-NES cells corresponded to 49.2% of that of implanted cells. Transplanted cells expressed markers of neuroblasts and mature and GABAergic neurons. Cell-grafted rats exhibited less activated microglia/macrophages in injured cortex and neuronal loss was mitigated. Conclusions: Our study provides the first evidence that grafted human iPSCs survive, differentiate to neurons and ameliorate functional deficits in stroke-injured aged brain. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Restorative Neurology and Neuroscience
volume
32
issue
4
pages
547 - 558
publisher
IOS Press
external identifiers
  • pmid:24916776
  • wos:000340031000009
  • scopus:84908294733
ISSN
1878-3627
DOI
10.3233/RNN-140404
language
English
LU publication?
yes
id
80061e04-0011-4ba5-b0dd-ad7b713314f3 (old id 4528889)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24916776?dopt=Abstract
date added to LUP
2016-04-01 10:28:31
date last changed
2025-04-04 14:19:01
@article{80061e04-0011-4ba5-b0dd-ad7b713314f3,
  abstract     = {{Purpose: Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke. Methods: Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage. After 48 h, animals were transplanted intracortically with human iPSC-derived long-term neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke and were vehicle-injected. Results: Cell-grafted animals performed better than vehicle-injected recipients in cylinder test at 4 and 7 weeks. At 8 weeks, cell proliferation was low (0.7 %) and number of hiPSC-lt-NES cells corresponded to 49.2% of that of implanted cells. Transplanted cells expressed markers of neuroblasts and mature and GABAergic neurons. Cell-grafted rats exhibited less activated microglia/macrophages in injured cortex and neuronal loss was mitigated. Conclusions: Our study provides the first evidence that grafted human iPSCs survive, differentiate to neurons and ameliorate functional deficits in stroke-injured aged brain.}},
  author       = {{Tatarishvili, Jemal and Oki, Koichi and Monni, Emanuela and Koch, Philipp and Memanishvili, Tamar and Buga, Ana-Maria and Verma, Vivek and Popa-Wagner, Aurel and Brüstle, Oliver and Lindvall, Olle and Kokaia, Zaal}},
  issn         = {{1878-3627}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{547--558}},
  publisher    = {{IOS Press}},
  series       = {{Restorative Neurology and Neuroscience}},
  title        = {{Human induced pluripotent stem cells improve recovery in stroke-injured aged rats.}},
  url          = {{http://dx.doi.org/10.3233/RNN-140404}},
  doi          = {{10.3233/RNN-140404}},
  volume       = {{32}},
  year         = {{2014}},
}